Extracellular Signal-regulated Kinase 1/2 is Involved in the Activation of NADPH Oxidase Induced by FMLP Receptor but not by Complement Receptor 3 in Rat Neutrophils

Abstract

This experiment was performed to clarify the role of extracellular signal-regulated kinase, ERK1/2, in NADPH oxidase-dependent O₂^- production in rat peritoneal neutrophils. When neutrophils were exposed to N-formyl-methionyl-leucyl-phenylalanine (fMLP) to stimulate an N-formyl peptide receptor, not only the production of O₂^- but also the activation of ERK1/2 was observed. The translocation of an NADPH oxidase component, p47^phox, from cytosol to membrane also occurred in neutrophils stimulated with fMLP. U0126, an ERK1/2 kinase inhibitor, inhibited both the production of O₂^- and the translocation of p47^phox elicited by fMLP. On the other hand, when complement receptor 3 of neutrophils was stimulated with opsonized zymosan (OZ), weaker activation of ERK1/2 than that by fMLP was observed. In this case, U0126 showed no inhibition against the production of O₂^- and slight inhibition against the translocation of p47^phox. Large inhibition against the OZ-induced production of O₂^- was only observed in neutrophils treated with GF109203X, a PKC inhibitor. The present study indicates that receptor dependence exists in the ERK1/2 signaling pathway leading to the activation of NADPH oxidase.

• CR3
• ERK1/2
• fMLP
• NADPH oxidase
• Neutrophil
• p47